The impact of endogenous dopamine on in vivo measurement of D2 receptors in humans was evaluated with SPECT by comparing in 9 healthy volunteers the binding potenial (BP) of [123I']IBZM before and after acute dopamine depletion. Dopamine depletion was achieved by administration of the tyrosine hydorxylase inhimitor alpha-methyl-para-tyrosine (AMPT, 1 g QID for two days). AMPT increased [123I]IBZM by 28+16% (mean + DS,n=9). Experiments in rodents with a similar time course showed that this effect was due to removal of endogenous dopamaine rather D2 receptor upregulation. Thus, D2 receptors are significantly occupied by dopamine in the resting state in humans. This paradigm will be extended over the next year to patients with schizophrenia to assess whether patients have an abnormal level of basal D2 occupancy by dopamine compared to healthy subjects.